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Biomedical subjects

D M Murphy

Publications and source records attributed to D M Murphy.

At least 19 recordsLinked to original sources
PubMed2006

Observations of mercury-containing aerosols.

In situ analyses with a laser ionization mass spectrometer have shown that a large fraction of aerosols in the bottom few kilometers of the stratosphere contain small amounts of mercury (1). Electron microscopy of particles collected near the tropopause has also detected mercury. The distribution of mercury onto many particles, including those less than 20 nm in diameter, indicates that the mercury is from local condensation of mercury compounds onto particles rather than transport of mercury-rich aerosols from surface sources. Although the results are only semiquantitative, they suggest that most of the mercury in the lower stratosphere is converted into the particulate phase. Mercury-containing particles were present at both middle latitudes and the tropics in two seasons. There is therefore good reason to believe that particulate mercury above the tropopause is global and could affect the atmospheric lifetime of mercury. There are indications that bromine and/ or iodine may be involved in the conversion of mercury from the gas to particle phase. Measurements at altitudes below 5 km did not find mercury in any particles despite sampling some particles that clearly originated in the stratosphere. This indicates that the particulate mercury from the lower stratosphere may be volatile enough to evaporate or decompose once particles reach warmer temperatures.

Aerosols↗
PubMed2006

Pseudomembranous colitis in four patients with cystic fibrosis following lung transplantation.

Pseudomembranous colitis is an uncommon complication in patients with cystic fibrosis, despite the use of multiple high-dose antibiotic regimens and the frequency of hospital admissions. Four patients from a total of 137 patients with cystic fibrosis undergoing lung transplantation are described who developed fulminant pseudomembranous colitis. Initial presentation was variable and the mortality rate was 50% despite urgent colectomy. In one case the presenting abdominal distension was thought to be due to meconium ileus equivalent. It is concluded that Clostridium difficile colitis may be a difficult diagnosis in patients with cystic fibrosis and follows a fulminant course after lung transplantation.

Adult↗
PubMed2005

Pepsin like activity in bronchoalveolar lavage fluid is suggestive of gastric aspiration in lung allografts.

BACKGROUND: A biologically plausible link between gastro-oesophageal reflux (GOR), aspiration, and lung allograft dysfunction has been suggested, but there is no systematic evidence indicating the presence of gastric contents in the lung. We have tested the hypothesis that pepsin, as a marker of aspiration, is detectable in bronchoalveolar lavage (BAL) fluid of allograft recipients who had not reported symptoms of GOR. METHODS: Standardised 3 x 60 ml surveillance BAL fluid samples from 13 chronologically sequential stable lung allograft recipients without chronic rejection (10 patients treated with a prophylactic proton pump inhibitor) were studied. Lavage supernatants were assayed by an ELISA based on a monospecific goat antibody for pepsin/pepsinogen. Pepsin levels were compared with those from four normal volunteer controls. RESULTS: Pepsin levels were measurable in all allograft recipients, in keeping with gastric aspiration (median 109 ng/ml (range 35-1375)). In the control group the pepsin levels were below the limit of detection. Treatment with a proton pump inhibitor was not correlated with pepsin levels. There was no correlation between BAL fluid neutrophils and pepsin levels. CONCLUSION: These data demonstrate lung epithelial lining fluid concentrations of pepsin in lung allograft recipients which are much higher than blood reference levels, with no detectable pepsin in controls. This provides direct evidence of gastric aspiration, which is potentially injurious to the allograft.

Adult↗
PubMed2005

Phenotype of airway epithelial cells suggests epithelial to mesenchymal cell transition in clinically stable lung transplant recipients.

BACKGROUND: Obliterative bronchiolitis in chronic rejection of lung allografts is characterised by airway epithelial damage and fibrosis. The process whereby normal epithelium is lost and replaced by fibroblastic scar tissue is poorly understood, but recent findings suggest that epithelial cells can become fibroblasts through epithelial-mesenchymal transition (EMT). It is hypothesised that EMT occurs in lung allografts and plays a potential role in airway remodelling. METHODS: Sixteen stable lung transplant recipients underwent bronchoscopy with bronchoalveolar lavage (BAL), endobronchial biopsies, and bronchial brushings. Biopsy sections were stained for the fibroblast marker S100A4. Brushings were cultured on collagen, stained with anti-S100A4, and examined for further EMT markers including matrix metalloproteinase (MMP) zymographic activity and epithelial invasion through collagen coated filters. RESULTS: A median 15% (0-48%) of the biopsy epithelium stained for S100A4 in stable lung transplant recipients and MMP-7 co-localisation was observed. In non-stimulated epithelial cultures from lung allografts, S100A4 staining was identified with MMP-2 and MMP-9 production and zymographic activity. MMP total protein and activity was increased following stimulation with transforming growth factor (TGF)-beta1. Non-stimulated transplant epithelial cells were invasive and penetration of collagen coated filters increased following TGF-beta1 stimulation. CONCLUSIONS: This study provides evidence of EMT markers in lung allografts of patients without loss of lung function. The EMT process may represent a final common pathway following injury in more common diseases characterised by airway remodelling.

Adult↗
PubMed2005

Primary airway epithelial cell culture from lung transplant recipients.

Long-term survival in lung transplantation is limited by the development of obliterative bronchiolitis, a condition characterised by inflammation, epithelial injury, fibroproliferation and obliteration of bronchioles leading to airflow obstruction. To investigate the role of the bronchial epithelium in the pathogenesis of obliterative bronchiolitis the current study aimed to establish primary bronchial epithelial cell cultures (PBEC) from lung allografts. Four to six bronchial brushings were obtained from sub-segmental bronchi of lung allografts. Cells were seeded onto collagen-coated plates and grown to confluence in bronchial epithelial growth medium. Bronchial brushings (n=33) were obtained from 27 patients. PBECs were grown to confluence from 12 out of 33 (39%) brushings. Failure to reach confluence was due to early innate infection. Bacteria were usually isolated from both bronchoalveolar lavage and culture media, but a separate population was identified in culture media only. Primary culture of bronchial epithelial cells from lung transplant recipients is feasible, despite a high rate of early, patient-derived infection. Latent infection of the allograft, identified only by bronchial brushings, may itself be a persistent stimulus for epithelial injury. This technique facilitates future mechanistic studies of airway epithelial responses in the pathogenesis of obliterative bronchiolitis.

Adolescent↗
PubMed2004

A machine for the preliminary investigation of design features influencing the wear behaviour of knee prostheses.

Degradation of tibial inserts in vivo has been found to be multifactorial in nature, resulting in a complex interaction of many variables. A range of kinematic conditions occurs at the tibio-femoral interface, giving rise to various degrees of rolling and sliding at this interface. The movement of the tibio-femoral contact point may be an influential factor in the overall wear of ultra-high molecular weight polyethylene (UHMWPE) tibial components. As part of this study a three-station wear-test machine was designed and built to investigate the influence of rolling and sliding on the wear behaviour of specific design aspects of contemporary knee prostheses. Using the machine, it is possible to monitor the effect of various slide roll ratios on the performance of contemporary bearing designs from a geometrical and materials perspective.

Arthroplasty, Replacement, Knee↗
PubMed2003

Measurements of the concentration and composition of nuclei for cirrus formation.

This article addresses the need for new data on indirect effects of natural and anthropogenic aerosol particles on atmospheric ice clouds. Simultaneous measurements of the concentration and composition of tropospheric aerosol particles capable of initiating ice in cold (cirrus) clouds are reported. Measurements support that cirrus formation occurs both by heterogeneous nucleation by insoluble particles and homogeneous (spontaneous) freezing of particles containing solutions. Heterogeneous ice nuclei concentrations in the cirrus regime depend on temperature, relative humidity, and the concentrations and physical and chemical properties of aerosol particles. The cirrus-active concentrations of heterogeneous nuclei measured in November over the western U.S. were <0.03 cm-3. Considering previous modeling studies, this result suggests a predominant potential impact of these nuclei on cirrus formed by slow, large-scale lifting or small cooling rates, including subvisual cirrus. The most common heterogeneous ice nuclei were identified as relatively pure mineral dusts and metallic particles, some of which may have origin through anthropogenic processes. Homogeneous freezing of large numbers of particles was detected above a critical relative humidity along with a simultaneous transition in nuclei composition toward that of the sulfate-dominated total aerosol population. The temperature and humidity conditions of the homogeneous nucleation transition were reasonably consistent with expectations based on previous theoretical and laboratory studies but were highly variable. The strong presence of certain organic pollutants was particularly noted to be associated with impedance of homogeneous freezing.

Atmosphere↗
PubMed2002

Is mechanical bowel preparation necessary in patients undergoing cystectomy and urinary diversion?

OBJECTIVE: To compare the surgical outcome in patients with or with no bowel preparation before cystectomy and ileal conduit urinary diversion, specifically assessing local and systemic complications. PATIENTS AND METHODS: All patients undergoing cystectomy and ileal conduit urinary diversion between January 1991 and December 1999 were assessed retrospectively. Twenty-two receive no bowel preparation (group 1) and were compared with 64 who had (group 2). Patients had similar demographic characteristics, stage and grade of tumour. Patients in group 2 received a standard 4-day bowel preparation and group 1 received no lavage or enemas. All patients underwent a standard iliac and obturator lymph node dissection, and cystoprostatectomy or anterior exenteration and ileal conduit urinary diversion. All patients received intraoperative metronidazole and gentamicin intravenously, and two further doses after surgery. RESULTS: Deaths after surgery were comparable in the two groups (two in group 1 and four in group 2) and the incidence of wound infection was similar (three and seven, respectively). There were no significant differences between the respective groups for fistula and anastomotic dehiscence (two and six) or sepsis (three and six). Group 2 had a higher incidence of wound dehiscence (one) than in group 1 (none). The incidence of prolonged postoperative ileus was lower in group 1 (one vs 12), as was the length of hospital stay (31.6 days vs 22.8 days). CONCLUSIONS: Bowel preparation had no advantage for the surgical outcome but it increased the length of hospital stay.

Aged↗
PubMed2001

Ablation, flux, and atmospheric implications of meteors inferred from stratospheric aerosol.

Single-particle analyses of stratospheric aerosol show that about half of the particles contain 0.5 to 1.0 weight percent meteoritic iron by mass, requiring a total extraterrestrial influx of 8 to 38 gigagrams per year. The sodium/iron ratio in these stratospheric particles is higher and the magnesium/iron and calcium/iron ratios are lower than in chondritic meteorites, implying that the fraction of material that is ablated must lie at the low end of previous estimates and that the extraterrestrial component that resides in the mesosphere and stratosphere is not of chondritic composition.

Journal Article↗
PubMed2001

Distinct protein sorting and localization to premelanosomes, melanosomes, and lysosomes in pigmented melanocytic cells.

Melanosomes and premelanosomes are lysosome-related organelles with a unique structure and cohort of resident proteins. We have positioned these organelles relative to endosomes and lysosomes in pigmented melanoma cells and melanocytes. Melanosome resident proteins Pmel17 and TRP1 localized to separate vesicular structures that were distinct from those enriched in lysosomal proteins. In immunogold-labeled ultrathin cryosections, Pmel17 was most enriched along the intralumenal striations of premelanosomes. Increased pigmentation was accompanied by a decrease in Pmel17 and by an increase in TRP1 in the limiting membrane. Both proteins were largely excluded from lysosomal compartments enriched in LAMP1 and cathepsin D. By kinetic analysis of fluid phase uptake and immunogold labeling, premelanosomal proteins segregated from endocytic markers within an unusual endosomal compartment. This compartment contained Pmel17, was accessed by BSA-gold after 15 min, was acidic, and displayed a cytoplasmic planar coat that contained clathrin. Our results indicate that premelanosomes and melanosomes represent a distinct lineage of organelles, separable from conventional endosomes and lysosomes within pigmented cells. Furthermore, they implicate an unusual clathrin-coated endosomal compartment as a site from which proteins destined for premelanosomes and lysosomes are sorted.

Clathrin-Coated Vesicles↗
PubMed2001

Successful transplantation of kidneys from a donor with HELLP syndrome-related death.

We report on the successful use of kidneys procured from a donor with HELLP syndrome. The use of organs from a donor with HELLP syndrome has not been reported previously, perhaps because of the renal complications associated with it. Both recipients have been doing well since renal transplantation, with immediate graft function and acceptable graft function at 2 years of follow-up. In view of the continuing shortage of cadaveric kidneys for transplantation, this report highlights how organs from "marginal" donors should not be discarded without worthy consideration.

Adult↗
PubMed2001

The epidemiology of invasive pneumococcal disease in children in Far North Queensland.

OBJECTIVES: To describe the epidemiology of invasive pneumococcal disease in children under 5 years of age in Far North Queensland and to examine the potential impact of a seven- and 11-valent conjugate pneumococcal vaccine. METHODS: A review of all cases of invasive pneumococcal disease in children under 5 years of age in Far North Queensland over a 9 year period (1992-2000). The distribution of the serotypes of isolates causing invasive pneumococcal disease was compared with the serotypes contained in the two vaccines. RESULTS: The annual incidence in indigenous and non-indigenous children under 5 years of age was 163 (95% confidence interval (CI) 122-213) and 42 (95% CI 31-55) cases per 100 000 children, respectively. For children under 2 years of age, these figures were 297 (95% CI 208-411) and 71 (95% CI 49-100), respectively. There was a greater variety of serotypes isolated from indigenous children (n=17) than from non-indigenous children (n=9; P < 0.01). The serotypes within the seven-valent vaccine accounted for 62% (95% CI 46-75%) and 88% (95% CI 76-95%) of the isolates from indigenous and non-indigenous children, respectively (P < 0.01). Serotypes within the 11-valent vaccine accounted for 72% (95% CI 57-84%) of the isolates from indigenous children under 5 years of age, but did not account for any extra isolates from non-indigenous children. CONCLUSION: Although the seven- and 11-valent conjugate pneumococcal vaccines cover only approximately 60 and 70%, respectively, of the isolates that cause invasive disease in indigenous children in Far North Queensland, they nevertheless have the potential to prevent much morbidity in and hospitalization of these children. It will be essential to maintain surveillance following the introduction of conjugate pneumococcal vaccines so as to monitor changes in the incidence of invasive pneumococcal disease, particularly in high-risk children.

Age Distribution↗
PubMed2001

The(13)C-octanoic acid breath test for detection of effects of meal composition on the rate of solid-phase gastric emptying in ponies.

The aim of this study was to apply the(13)C-octanoic acid breath test for detection of alterations in the rate of solid-phase gastric emptying, induced by changes in test meal composition, in ponies. After a 14 hour fast the ponies (n = 4) ingested a test meal with 0, 35 or 70 ml soya oil, and labelled with 250 mg(13)C-octanoic acid. Each pony was given each of the three test meals on three separate occasions, in a randomised order. Exhaled breath samples were collected for 12 hours after ingestion of the test meal. Breath samples were analysed by continuous flow isotope ratio mass spectrometry. Three indices of breath(13)C-enrichment were computed, half-dose recovery time (t 1/2), gastric emptying coefficient (GEC) and time to peak breath(13)C-excretion t(max). The(13)C-octanoic acid breath test was a reliable means of assessing the significantly decreased rate of gastric emptying in the pony, associated with addition of soya oil to the test meal.

Animal Feed↗
PubMed2001

The initial coverage and impact of the pneumococcal and influenza vaccination program for at-risk indigenous adults in Far North Queensland.

OBJECTIVES: To describe the initial coverage and impact of a pneumococcal and influenza vaccination program for at-risk Indigenous adults in Far North Queensland that formally commenced in 1996. DESIGN: Ascertainment of vaccine coverages, and prospective laboratory surveillance of invasive pneumococcal disease occurring in Indigenous adults in the region. MAIN OUTCOME MEASURES: Coverages of the first doses of both vaccines administered since 1995, and the incidence of invasive pneumococcal disease in Indigenous adults in the region between 1993-2000. RESULTS: Most (96% and 73%) of the Indigenous adults > or = 50 years of age received influenza and pneumococcal vaccines, respectively, for the first time between 1995-2000. Assuming that either 33% or 50% of Indigenous adults 15-49 years of age in Far North Queensland were eligible for vaccination, then either 109% or 72% of this population received influenza vaccine, and either 75% or 50% received pneumococcal vaccine, respectively, for the first time between 1995-2000. The incidence of vaccine-preventable invasive pneumococcal disease fell from 111 (95% confidence interval [CI] 77-154) cases per 100,000 per year in 1993/94 to 28 (95% CI 13-53) cases per 100,000 per year in 1999-2000 (p<0.05). CONCLUSION: Although there was a significant decline in the incidence of invasive pneumococcal disease, the vaccine coverages after five years of the program were suboptimal. Because of the difficulties in targeting the 15-49 years age group and because of unrecognised risk factors, we suggest that a universal Indigenous adult pneumococcal and influenza vaccination program should be considered.

Adolescent↗